Plasmodium falciparum is undoubtedly one of the most influential organisms in human history. This unicellular parasite is one of the main species responsible for malaria, a disease that's killed tens of billions of humans and continues to infect over 200 million people each year. 

But how did our unfortunate relationship with this parasite start? A new study reveals an important chapter of this story can be traced back to an unlikely encounter between two parasites some 50,000 years ago and a rare genetic event that allowed the infection to jump from gorillas to humans. 

All of the malaria parasites originated in African great apes. However, somewhere along the line, some obtained the ability to switch host from gorillas to humans. There are seven Plasmodium parasite species that cause malaria and five species that can infect humans, although just two of these species – P. falciparum and P. vivax – are responsible for the vast majority of human infections. P. falciparum accounted for 99.7 percent of malaria cases in Africa in 2017.

To understand how this decisive leap from gorilla to humans occurred, scientists from the Wellcome Sanger Institute used ancestral sequence reconstruction to study the molecular evolution of a 50,000-year-old P. falciparum ancestor. Reporting in the journal PLOS Biology, the researchers focused on RH5, a gene that codes for a protein that binds to a protein receptor in human red blood cells and allows the parasite to invade.

The ancestral RH5 protein appeared to have the dual ability to bind to both gorilla and human basigin, allowing the parasite to infect the red blood cells of both species. 

Remarkably, it seems to have obtained this ability by a stroke of luck.

The researchers argue that two different types of Plasmodium parasites happened to both infect a gorilla cell simultaneously and they exchanged some genetic material between themselves through a process known as introgression. The result was a Plasmodium parasite equipped with the genes that allowed it to infect both gorillas and humans. 

Further analysis then revealed the mutations was that meant the parasite was no longer able to bind to gorilla basigin, explaining how P. falciparum became restricted to humans only.

"It’s fascinating to be able to ‘resurrect’ ancestral genes such as the one which allowed Plasmodium falciparum to jump from gorillas to humans. We’ve discovered not only how a species host switch has occurred, but the individual mutation which has then restricted P. falciparum to a single host species," Dr Franck Prugnolle, co-lead author from the University of Montpellier, said in a statement.

Not only does this discovery highlight the history of how one of the world's most deadly diseases came to infect humans, but it also provides insights into how pathogens can make the fateful leap from one species to another.

Of course, malaria is far from the only disease that humans have acquired from our great ape relatives. Other examples of modern zoonotic diseases that have bridged the gap from non-human primates to humans include Ebola, Zika, and – perhaps most famously – human immunodeficiency viruses (HIV).